Therapeutic effect of antimicrobial drugs against experimental infections due toYersinia pestis in mice

Although there are effective antibacterial agents against plague, newer antibacterial agents have been developed which show more potent activity against other bacterial organisms, but have not been tested againstYersinia pestis. A strain ofYersinia pestis was selected (no. 22; National Institute of Infectious Diseases, Tokyo, Japan) that caused a systemic infection in mice.Y. pestis no. 22 was intraperitoneally inoculated into DDY-strain mice, and 13 oral or 6 injectable antibacterial drugs given to the infected mice at varying doses 1 and 24 hours after infection. Levofloxacin, sparfloxacin and ofloxacin were the most effective oral agents against the infection, and prulifloxacin and pazufloxacin were also effective but to a lesser extent. Also, gentamicin and arbekacin were the most potent injectable antibacterial agents againstY. pestis. These results suggest that there are several new drugs, both oral and injectable, which exert excellent in vivo antibacterial activity against a mouse infection model and may be useful for the clinical treatment of plague.     

Thoracic duct cyst in supraclavicular region.

A 28-year-old female attended an outpatient clinic in October, 1989, because of a tumor in the left supraclavicular fossa, detected in a health examination. Following exploratory puncture of the tumor which yielded milky-white fluid, suggesting a cyst in the thoracic duct, she was admitted to our department. The cyst was unilocular measuring about 6 cm in diameter, and the fluid content was chyle-rich in lipids. Lymphography demonstrated a lymphatic structure adjacent to the lesion and scattered lymph vessels on the cyst surface. On November 16 the cyst was resected. A restiform structure was observed between the cyst and the thoracic duct, but the presence or absence of communication was unclear. The histological diagnosis was thoracic duct cyst. Thoracic duct cyst occurring in the cervical region is very rare. Our case may provide useful information as to its pathogenesis and the mode of retention of cyst fluid.     

Detection of proteinous toxins using the Bio-Threat Alert system, part 3: effects of heat pretreatment and interfering substances

We previously reported that the Guardian Bio-Threat Alert (BTA) system could detect (detection limit: about 0.1 μg/ml) staphylococcal enterotoxin B (SEB), botulinum toxins (BTX) A and B, and ricin, with no interference by white-powdered materials or colored matrices. In this study, the capability of the BTA system was further assessed. With 10 min of preheating at 60°C, all toxins could be detected, but with preheating at 80°C, BTX A and B and ricin became undetectable. About 20% SEB could be detected after heating at 80°C, but this detection ability was completely removed after heating at 100°C. The effects of chemicals usually used for decontamination, such as sodium hypochlorite, hydrogen peroxide, formaldehyde, and sodium nitrite, on the detectability of SEB, BTX A, or ricin in the BTA system were also tested. The concentrations giving 50% line intensity for SEB, BTX A, and ricin were 3.1, 11, and 15 μM for sodium hypochlorite and 88, 210, and 60 mM for formaldehyde, respectively. The addition of hydrogen peroxide or sodium nitrite did not decrease the detectability even when used at high concentrations.     

Immunological detection of phosphotyrosine-containing proteins in rat livers after insulin injection.

Tyrosine-phosphorylated proteins in Triton X-100-solubilized fractions of rat livers were examined by immunoblotting with anti-phosphotyrosine antibodies. After 2 min of insulin injection via the portal vein into livers, three major bands of 170,000, 140,000, and 95,000 Mr were stimulated. Because the incubation of nitrocellulose membrane with anti-phosphotyrosine antibodies in the presence of 40 mM phosphotyrosine completely abolished these bands, the anti-phosphotyrosine antibodies appear to recognize the phosphotyrosine residues of these proteins. Insulin injection (2-2000 micrograms) very quickly stimulated the tyrosine phosphorylation of these proteins in a dose-dependent fashion. In contrast, insulinlike growth factor I or epidermal growth factor injection had little effect in stimulating the tyrosine phosphorylation of these proteins. Because anti-insulin-receptor antibodies immunoprecipitated a tyrosine-phosphorylated 95,000-Mr protein, this protein must be the beta-subunit of the insulin receptor; i.e., the beta-subunit of the insulin receptor and two other proteins were phosphorylated at tyrosine residues in vivo by insulin injection. These data suggest that the tyrosine phosphorylation and tyrosine kinase activity of the insulin receptor may have important roles in in vivo insulin action.     

Animal study on the role of serotonin in depression

1. In our series of experiments the role of serotonin in human depression was studied by using animal models of depression.

2. The results of these studies support the hypothesis that some types of human depression may be primarily due to an excessive transmission of serotonin at the synapse.     

Attenuated sympathetic tone augments nitrous oxide-induced myocardial depression during high-dose fentanyl anaesthesia in dogs

The purpose of this study was to determine whether centrally mediated sympathetic tone exerts compensatory effects on nitrous oxide-induced myocardial depression during high-dose fentanyl anaesthesia. The cardiovascular responses to 60 minutes of nitrous oxide administration after fentanyl, 100 micrograms.kg-1, were examined in 18 dogs with or without autonomic blockade induced by hexamethonium. Decreases of cardiac output and left ventricular stroke work were significantly greater in dogs with autonomic blockade (n = 9) by about 20 per cent of baseline values than in dogs without autonomic blockade (n = 9) at 30, 45, and 60 min. Similarly, left ventricular dP/dt was reduced more in dogs with autonomic blockade than in dogs without autonomic blockade, but this difference was only significant at the 60-min period. It is concluded that the sympathetic nervous system provides partial compensation for myocardial depression induced by nitrous oxide in the presence of high-dose fentanyl, suggesting that large doses of fentanyl do not ablate the centrally mediated sympathomimetic effects of nitrous oxide.     

Lower extremity reconstruction after necrotising fasciitis and necrotic skin lesions using a porcine-derived skin substitute.

Seven consecutive clinical cases of necrotising fasciitis or necrotic skin lesions (42-78 years old; average 65.0 years of age, three females and four males) due to group A Streptococcus, group B Streptococcus, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in the lower extremities, who demonstrated rapid systemic symptoms, were investigated for the usefulness of a bilayer artificial dermis, derived from porcine tendons, over 4 +/- 2.4 years (1-7 years). All surgical debridement was confirmed as sufficiently deep and wide for clinically infected lesions and artificial dermis was applied to all wounds. The average interval to secondary split-thickness skin grafting was about 17.5 days (17.5 +/- 2.44 days, 21 days max., 14 days min.) and the average thickness was 0.009 +/- 0.0022 in. (range: 0.006 - 0.012 in.). No clinical problems were noted during the application of the artificial dermis and the subsequent skin grafting. Since, the donated skin graft was thin, the morbidity was minimised. The use of artificial dermis after extensive surgical debridement in necrotising fasciitis was easy and effective. Local or systemic infection was negligible.     

Changes in Properties of Spinal Dorsal Horn Neurons and Their Sensitivity to Morphine after Spinal Cord Injury in the Rat

Background: To gain a better understanding of spinal cord injury (SCI)-induced central neuropathic pain, the authors investigated changes in properties of spinal dorsal horn neurons located rostrally and caudally to the lesion and their sensitivity to morphine in rats after SCI.

Methods: The right spinal cord of Sprague-Dawley rats was hemisected at the level of L2. At 10 to 14 days after the SCI, when mechanical hyperalgesia/allodynia had fully developed, spontaneous activity and evoked responses to mechanical stimuli of wide-dynamic-range (WDR) and high-threshold neurons rostral and caudal to the lesion were recorded. Effects of cumulative doses of systemic (0.1-3 mg/kg) and spinal (0.1-5 [mu]g) administration of morphine on spontaneous activity and evoked responses to the stimuli of the neurons were evaluated.

Results: Spontaneous activity significantly increased in WDR neurons both rostral and caudal to the SCI site, but high-frequency background discharges with burst patterns were only observed in neurons rostral to the SCI site. Significant increases in responses to the mechanical stimuli were seen both in WDR and high-threshold neurons located both rostrally and caudally to the lesion. The responses to nonnoxious and noxious stimuli were significantly greater in caudal WDR neurons than in rostral WDR neurons. In contrast, the responses to pinch stimuli were significantly higher in rostral high-threshold neurons than those in caudal high-threshold neurons. Systemically administered morphine had a greater effect on responses to nonnoxious and noxious stimuli of rostral WDR neurons than those of caudal WDR neurons. Spinally administered morphine significantly suppressed responses of WDR neurons in SCI animals to nonnoxious stimuli compared with those in sham-operated control animals.